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Abstract Alcohol use disorder (AUD) represents a public health crisis with few FDA-approved medications for its treatment. Growing evidence supports the key role of the bidirectional communication between the gut microbiota and the central nervous system (CNS) during the initiation and progression of alcohol use disorder. Among the different protective molecules that could mediate this communication, short chain fatty acids (SCFAs) have emerged as attractive candidates, since these gut microbiota-derived molecules have multi-target effects that could normalize several of the functional and structural parameters altered by chronic alcohol abuse. The present study, conducted in male alcohol-preferring UChB rats, shows that the initiation of voluntary ethanol intake was inhibited in 85% by the intragastric administration of a combination of SCFAs (acetate, propionate and butyrate) given before ethanol exposure, while SCFAs administration after two months of ethanol intake induced a 90% reduction in its consumption. These SCFAs therapeutic effects were associated with (1) a significant reduction of ethanol-induced intestinal inflammation and damage; (2) reduction of plasma lipopolysaccharide levels and hepatic inflammation; (3) reduction of ethanol-induced astrocyte and microglia activation; and (4) attenuation of the ethanol-induced gene expression changes within the nucleus accumbens. Finally, we determined that among the different SCFAs evaluated, butyrate was the most potent, reducing chronic ethanol intake in a dose–response manner. These findings support a key role of SCFAs, and especially butyrate, in regulating AUD, providing a simple, inexpensive, and safe approach as a preventive and intervention-based strategy to address this devastating disease.

Abstract Background Insecticide-treated nets (ITNs) are the most commonly deployed tools for controlling malaria transmission in sub-Saharan Africa. However, some reports associate multiple alternative uses of nets with poor disposal practices, prompting this study to assess existing alternative uses and disposal practices of old ITNs in Burkina Faso after four universal distribution campaigns. Methods A quantitative survey combined with qualitative data collection was used to describe existing alternative uses and disposal practices for old ITNs in households from selected study sites in the three climatic zones of Burkina Faso. A survey questionnaire was distributed to 3,780 participants, and 12 focus groups were held to elucidate responses regarding existing disposal practices and alternative uses of ITNs. Results Of the 3780 households surveyed, 87.4% (3,330) reported having disposed of their ITNs when they were no longer usable due to age or wear. The most commonly cited disposal methods included alternative uses (67.4%), disposal with other garbage (61.4%), and burying (9%). In addition, the most common alternative uses included fencing for crops and seedlings (51.8%); ropes for tying items (40.4%); animal protection fencing (17.8%); house fencing (16.8%); bed covers (13.3%) and curtains for doors or windows (12.6%). Furthermore, trends in ITNs disposal mechanisms and alternative uses differed between study sites in each climate zone. All these ITNs disposal mechanisms and the different types of alternative use of old ITNs were confirmed in the focus group discussions. Conclusion The findings underscore the need for comprehensive strategies to manage the disposal and repurposing of old ITNs in Burkina Faso. Addressing gaps in disposal guidelines, promoting safe and beneficial reuse practices, and actively involving communities in the decision-making process can help mitigate health risks associated with the improper disposal and repurposing of old insecticide-treated nets and improve the overall effectiveness of malaria control programmes. Through these efforts, both public health and environmental concerns can be addressed in a sustainable and collaborative manner.

Abstract Context Clinical data on transgender children and adolescents are scarce, and sample sizes often do not allow for comparisons according to sex assigned at birth. Besides, most gender identity clinics have pointed to a recent switch in favor of an increase in the number of adolescents assigned females at birth (AFAB) over assigned males at birth (AMAB). Method We collected data on sociodemographic characteristics, and psychiatric and social vulnerabilities according to sex assigned at birth for all youths who were treated at the French largest gender identity clinic. In addition, management modalities for gender transition were discussed in multidisciplinary concertation meetings. Results We collected data from 239 youths [162(68%) AFAB, 74(32%) AMAB, and 3(1%) intersex; mean age = 14.5(± 3.16) years]. The distribution of age at referral was better explained by two clusters (C1: N = 61, mean age = 11.3 years, with more AMAB; C2: N = 175, mean age = 15.9 years with more AFAB). 215(91%) youths had gender incongruence, with 32% reporting it before puberty. School drop-out, suicidality, depression, and anxiety were common and occurred significantly more often in the AFAB group. 178(74%) youths experienced social transition within the family, and 144(61%) at school [mean age = 15.13(± 2.06) years]. The social transition was more frequent in the AFAB group. Twenty-six (11%) youths received puberty blockers [mean age = 13.87(± 2.31) years], and 105(44%) received gender-affirming hormones [mean age = 16.87(± 1.4) years]. AMABs were more likely to take puberty blockers, and there was no difference in the proportion of AMAB and AFAB taking gender-affirming hormones. Surgical requests (mainly torsoplasty) were very rare. Conclusion Age at referral should be considered when exploring gender incongruence. During adolescence, we found that gender incongruence has substantial social and psychological effects, particularly on AFAB youths, possibly explaining their higher referral rates to specialized centers, as in other specialized clinics around the world.

Objective: Subclinical hyperthyroidism (SCH) is common and associated with atrial fibrillation (AF) risk in the elderly. Current guidelines rely on a low level of evidence. Methods: Randomized clinical trial including patients 50 years and older, with thyroid-stimulating hormone (TSH) 65 years or TSH < 0.1mU/L. Of 94 patients treated using radioiodine, 25% developed hypothyroidism during follow-up. Conclusion: Due to recruitment difficulties, this study failed to demonstrate that SCH treatment can significantly reduce the incidence of AF in patients older than 50 years with thyroid autonomy even if all the patients who developed AF maintained TSH

Abstract Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive. Here we show the impact of KDM6B mosaic brain knockout on the manifestation of different autistic-like phenotypes including repetitive behaviors, social interaction, and significant cognitive deficits. Moreover, KDM6B mosaic knockout display abnormalities in hippocampal excitatory synaptic transmission decreasing NMDA receptor mediated synaptic transmission and plasticity. Understanding the intricate interplay between epigenetic modifications and neuronal function may provide novel insights into the pathophysiology of ASD and potentially inform the development of targeted therapeutic interventions.

Abstract Background A quasi-experimental comparative trial will be designed in Burkina Faso. The study will compare the use and preferences for two groups types of insecticide-treated nets textile: polyester-based and polyethylene-based, according to their use and preferences in selected health districts. These health districts will be selected in three eco-climate zones (Sahelian, dry savannah and wet savannah) in the country. These findings will inform decisions on future net procurements for national malaria control programme in 2025. Methods Quantitative surveys and qualitative data collection will be carried out to gather information on the type of net textile most commonly used and preferred by the community. They will be performed between the end of the dry season and the early rainy season. The quantitative surveys involved household interviews with households and individuals’ questionnaires, while the qualitative data collection involved in-depth individual interviews and focus group discussions to explore and clarify some key evaluation criteria. A total of 9450 insecticide-treated nets were surveyed for quantitative survey purposes. For the qualitative study, 48 in-depth individual interviews and 12 focus group discussions were carried out. A mixed model approach combining the results from quantitative surveys and qualitative studies will be used for decision-making on the type of insecticide-treated net preference. Conclusion This methodological approach will be used by the National Malaria Control Programme to conduct this study on determinants of net use in Burkina Faso in order to provide robust evidence across diverse settings. This mixed-methods approach for data collection and analysis could be used in other countries to provide evidence that would help to increase the uptake of insecticide-treated nets, the main vector control tool in Africa.

Abstract Background Mother-to-child transmission of HIV during breastfeeding remains a challenge in low- and middle-income countries (LMIC). A prevention package was initiated during the highly attended 2nd visit of the Expanded Program of Immunisation (EPI-2) to identify the undiagnosed infants living with HIV and reduce the postnatal transmission of infant exposed to HIV. Methods PREVENIR-PEV is a non-randomized phase II clinical trial conducted at two health centres in Bobo Dioulasso (Burkina Faso). The study recruited mothers living with HIV aged 15 years and older with their singleton breastfed infants. During EPI-2 (at 8 weeks) and upon signature of the informed consent, a point-of-care early infant diagnosis (EID) was performed. HIV exposed uninfected (HEU) infants were followed-up until 12 months of age. High risk HEU infants (i.e., whose maternal viral load ≥ 1000 cp/mL at EPI-2 or M6) received an extended postnatal prophylaxis (PNP) with lamivudine until end of follow-up or the end of breastfeeding. Results Between 4 December 2019 and 4 December 2020, 118 mothers living with HIV-1 were identified, and 102 eligible mother/infant pairs had their infants tested for HIV EID. Six infants were newly diagnosed with HIV, and 96 HEU infants were followed-up for 10 months. Among the participants followed-up, all mothers were prescribed antiretrovirals. All 18 infants eligible for PNP at either EPI-2 or 6 months (M6) were initiated on lamivudine. No HIV transmission occurred, and no serious adverse events were reported in infants receiving lamivudine. Conclusions The PREVENIR-PEV prevention package integrated into existing care is safe and its implementation is feasible in a LMIC with a low HIV prevalence. More research is needed to target mother/infant pairs not adhering to the intervention proposed in this trial. Trial registration NCT03869944; first registered on 11/03/2019.

Background: Despite vaccination, patients receiving anti-CD20 monoclonal antibodies (mAbs) for multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD) have an increased risk of developing severe or protracted COVID-19. The aim of this study was to describe the effect of COVID-19 convalescent plasma (CCP) in patients with MS or NMOSD exposed to anti-CD20 and infected by SARS-CoV-2. Methods: This French national, retrospective cohort study was conducted between November 2020 and June 2023. Patients with MS or NMOSD, under anti-CD20 mAbs, with symptomatic COVID-19 and treated by CCP were screened. Protracted COVID-19 was defined by a duration of symptoms >21 days. The primary endpoint was the overall survival 30 days after CCP administration. Results: Ninety-two patients from 34 hospitals were included, 84 (91%) with MS and 8 (9%) with NMOSD. Overall, 30-day survival was 97% (IC95%: 91-99). SARS-CoV-2 viremia was positive in 47/75 (61%) patients before CCP versus 9/59 (15%) seven days post-CCP. In the 52 patients (57%) with protracted COVID-19, the duration of symptoms before CCP was 51 [28-69] days, including fever in 75% of cases, which disappeared in 100% of patients 7 days post-CCP. Conclusions: CCP could be a therapeutic option in patients exposed to anti-CD20 mAbs for inflammatory demyelinating disease, particularly in those with protracted COVID-19.

The aim of this study was to determine the prevalence of advanced hepatic fibrosis and to individualize using Bayesian analysis its associated risk factors in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) being cared for in three Alsatian cardio-metabolic health networks in the North East of France. Overall, 712 patients aged ≥18 years with a female predominance were included into a prospective, cross-sectional, and observational study. Advanced fibrosis and severe steatosis were evaluated using transient elastography (FibroScan®). The proportion of MASLD patients was 80% and 84% in women and men (difference -4.2% [-10.0; 1.9]), respectively. Advanced fibrosis was observed in 11% of patients, being more common in men (16.9%) than women (7.5%) (difference 9.4 [4.3-15.0]). Severe steatosis was also more common in men (74.9%) than women (63.4%) (difference 11.4 [4.2-18.2]). Only three of the tested variables were likely associated with advanced fibrosis: gender (OR: 1.78 [1.17-2.68]; Pr [OR >1] = 1), T2DM (OR: 1.54 [1-2.37]; Pr [OR >1] = 0.97) and hypertriglyceridemia (OR: 1.49 [0.97-2.27]; Pr (OR >1) = 0.97). In conclusion, this study confirmed the usefulness of assessing hepatic fibrosis in patients with metabolic dysfunction. Therefore, access to FibroScan® should be facilitated in all cardio-metabolic health networks.

IntroductionThe availability of large-scale multi-omic data has revolution-ized the study of cellular machinery, enabling a systematic understanding of biological processes. However, the integration of these datasets into Genome-Scale Models of Metabolism (GEMs) re-mains underexplored. Existing methods often link transcriptome and proteome data independently to reaction boundaries, providing models with estimated maximum reaction rates based on individual datasets. This independent approach, however, introduces uncertainties and inaccuracies.MethodsTo address these challenges, we applied a principal component analysis (PCA)-based approach to integrate transcriptome and proteome data. This method facilitates the reconstruction of context-specific models grounded in multi-omics data, enhancing their biological relevance and predictive capacity.ResultsUsing this approach, we successfully reconstructed an astrocyte GEM with improved prediction capabilities compared to state-of-the-art models available in the literature.DiscussionThese advancements underscore the potential of multi-omic inte-gration to refine metabolic modeling and its critical role in studying neurodegeneration and developing effective therapies.

Abstract Among strategies to limit ischemia/reperfusion (IR) injuries in transplantation, cell therapy using stem cells to condition/repair transplanted organs appears promising. We hypothesized that using a cell therapy based on extracellular vesicles (EVs) derived from urine progenitor cells (UPCs) during hypothermic and normothermic machine perfusion can prevent IR‐related kidney damage. We isolated and characterized porcine UPCs and their extracellular vesicles (EVs). Then these were used in an ex vivo porcine kidney preservation model. Kidneys were subjected to warm ischemia (32 min) and then preserved by hypothermic machine perfusion (HMP) for 24 h before 5 h of normothermic machine perfusion (NMP). Three groups were performed (n = 5–6): Group 1 (G1): HMP/vehicle + NMP/vehicle, Group 2 (G2): HMP/EVs + NMP/vehicle, Group 3 (G3): HMP/EVs + NMP/EVs. Porcine UPCs were successfully isolated from urine and fully characterized as well as their EVs which were found of expected size/phenotype. EVs injection during HMP alone, NMP alone, or both was feasible and safe and did not impact perfusion parameters. However, cell damage markers (LDH, ASAT) were decreased in G3 compared with G1, and G3 kidneys displayed a preserved tissue integrity with reduced tubular dilatation and inflammation notably. However, renal function indicators such as creatinine clearance measured for 5 h of normothermic perfusion or NGAL perfusate's level were not modified by EVs injection. Regarding perfusate analysis, metabolomic analyses and cytokine quantification showed an immunomodulation signature in G3 compared with G1 and highlighted potential metabolic targets. In vitro, EVs as well as perfusates from G3 partially recovered endothelial cell metabolic activity after hypoxia. Finally, RNA‐seq performed on kidney biopsies showed different profiles between G1 and G3 with regulation of potential IR targets of EVs therapy. We showed the feasibility/efficacy of UPC‐EVs for hypothermic/normothermic kidney conditioning before transplantation, paving the way for combining machine perfusion with EVs‐based cell therapy for organ conditioning. Highlights ·UPCs from porcine urine can be used to generate a cell therapy product based on extracellular vesicles (pUPC‐EVs). ·pUPC‐EVs injection during HMP and NMP decreases cell damage markers and has an immunomodulatory effect. ·pUPC‐EVs‐treated kidneys have distinct biochemical, metabolic, and transcriptomic profiles highlighting targets of interest. ·Our results pave the way for combining machine perfusion with EV‐based cell therapy for kidney conditioning.

Background and aim: Self-medication, commonplace in Ouagadougou, is facilitated by growing access to the Internet and social networks. This study analyzes the impact of these technologies on this practice and the public health challenges it poses. Methods: It was a descriptive cross-sectional study conducted from August 1 to October 31, 2023. The study included all people using self-medication during this period. We randomly selected on-call pharmacies to survey patients purchasing medication. Data were collected using electronic questionnaires via KoboToolbox software. A logistic regression model was used to identify factors associated with the practice of self-medication via the Internet. Results: We collected data from 697 people. Five hundred people (n=500) out of the 658 who used the Internet, i.e. 75.98%, admitted to having already looked for health-related information on the Internet. The rate of self-medication via the Internet was 55.20% (n=385). The average age for self-medication via the internet was 29.95±9.6 years [18 years - 70 years], with a sex ratio of 1.21. Self-medication via the Internet was noted among people with a higher level of education in 65% of cases. The final logistic regression model showed that lack of access to healthcare professionals, unbearable waiting times in maternity wards, and the high cost of consultation fees and prescribed medication were factors associated with the practice of self-medication via the internet. Conclusion: Our results show the need to implement strategies to improve quality of care and facilitate access to reliable data sources for populations

Introduction: SCLC has traditionally been considered to arise from toxic exposure factors, such as smoking. Recent evidence has revealed that germline mutations may also affect the development of SCLC; however, these alterations remain understudied. We sought to identify novel germline mutations in SCLC including germline copy number variations (CNVs) in our cohort of patients. Methods: We designed a custom hybrid-capture gene panel to evaluate germline alterations in 192 cancer-predisposition and frequently mutated genes in SCLC. We applied this panel to germline analysis of a treatment-naive cohort of 67 patients with SCLC at our institution. Subsequently, we annotated the variants using the American College of Medical Genetics criteria and further classified variants of uncertain significance using a set of in silico tools, including DeepMind AlphaMissense, MutationTaster, SIFT, and Polyphen2. Results: We identified American College of Medical Genetics pathogenic or likely pathogenic alterations in seven of 67 patients. Five (71%) were novel alterations (BCORL1, FANCC, ATR, and BBC3) and a novel CNV (SLFN11) with two (29%) previously described mutations (CHEK1 and BRIP1). We also identified 191 variants of uncertain significance in 60 of 67 patients, of which, depending on the in silico tool, 5% to 14% were predicted to be pathogenic. Patients with SCLC with the seven pathogenic alterations were observed to have a numerically longer overall survival (hazard ratio = 0.50) and progression-free survival (hazard ratio = 0.45) though not statistically significant compared with the remaining cohort. Conclusions: Our study identifies novel germline alterations, including a CNV, and provides additional evidence that germline factors could be important contributing factors to the development of SCLC.

Abstract Background The VPS50 protein functions in synaptic and dense core vesicle acidification, and perturbations of VPS50 function produce behavioral changes in Caenorhabditis elegans. Patients with mutations in VPS50 show severe developmental delay and intellectual disability, characteristics that have been associated with autism spectrum disorders (ASDs). The mechanisms that link VPS50 mutations to ASD are unknown. Results To examine the role of VPS50 in mammalian brain function and behavior, we used the CRISPR/Cas9 system to generate knockouts of VPS50 in both cultured murine cortical neurons and living mice. In cultured neurons, KO of VPS50 did not affect the number of synaptic vesicles but did cause mislocalization of the V-ATPase V1 domain pump and impaired synaptic activity, likely as a consequence of defects in vesicle acidification and vesicle content. In mice, mosaic KO of VPS50 in the hippocampus altered synaptic transmission and plasticity and generated robust cognitive impairments. Conclusions We propose that VPS50 functions as an accessory protein to aid the recruitment of the V-ATPase V1 domain to synaptic vesicles and in that way plays a crucial role in controlling synaptic vesicle acidification. Understanding the mechanisms controlling behaviors and synaptic function in ASD-associated mutations is pivotal for the development of targeted interventions, which may open new avenues for therapeutic strategies aimed at ASD and related conditions.

ABSTRACT The impact of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) rectal colonization in the development of subsequent infection after surgery is controversial. In particular, there is a lack of data in the context of hepato-pancreato-biliary (HPB) surgery. The objective of this study was to assess the prevalence of 3GCR-E intestinal carriage among patients undergoing elective HPB resection surgery and its impact on the incidence and etiology of surgical site infections (SSIs). This retrospective cohort study (January 2016–December 2022) was performed at Valme University Hospital (Seville, Spain). The inclusion criteria included (i) 18 years of age or older, (ii) undergoing elective HPB resection surgery, and (iii) availability of a periprocedural surveillance rectal swab culture to detect 3GCR-E. The prevalence of 3GCR-E intestinal carriage at elective HPB resection surgery was assessed, as well as SSI incidence at 30 days and possible associated factors. Two hundred nine patients were included. Eleven (5.3%) patients were colonized by 3GCR-E at baseline. According to 3GCR-E carriage status, 6 (55%) of the carriers developed SSI, whereas this occurred in 50 (25%) of non-carriers (P = 0.033). Likewise, the rates of SSI caused specifically by 3GCR-E were 83% (5 of 6) in 3GCR-E carriers and 6% (3 of 50) in non-carriers (P < 0.001). After multivariate analyses, 3GCR-E colonization at the time of surgery was identified as an independent predictor for developing SSI (adjusted odds ratio 4.63, 95% confidence interval: 1.177–18.232, P = 0.028). Despite a low prevalence of 3GCR-E intestinal carriage at surgery, 3GCR-E rectal colonization is associated with a higher risk of SSI among patients undergoing elective HPB resection surgery, with most SSIs being caused by the colonizing bacteria.IMPORTANCEIn this Spanish retrospective cohort study, previous 3GCR-E rectal colonization was associated with a higher risk of SSI after hepato-pancreato-biliary resection surgeries. Most of SSIs were caused by the colonizing bacteria, suggesting a rationale for adapted perioperative antibiotic prophylaxis in known 3GCR-E colonized patients.

Summary: Natural killer (NK) cells play a pivotal role against cancer, both by direct killing of malignant cells and by promoting adaptive immune response though cytokine and chemokine secretion. In the lung tumor microenvironment (TME), NK cells are scarce and dysfunctional. By conducting single-cell transcriptomic analysis of lung tumors, and exploring pseudotime, we uncovered that the intratumoral maturation trajectory of NK cells is disrupted in a tumor stage-dependent manner, ultimately resulting in the selective exclusion of the cytotoxic subset. Using functional assays, we observed intratumoral NK cell death and a reduction in cytotoxic capacities depending on the tumor stage. Finally, our analyses of human public dataset on lung cancer corroborate these findings, revealing a parallel dysfunctional maturation process of NK cells during tumor progression. These results highlight additional mechanisms by which tumor cells escape from NK cell cytotoxicity, therefore paving the way for tailored therapeutic strategies.

Background The optimal strategy in prosthetic heart valve thrombosis (PVT) remains controversial, with no randomized trials and conflicting observational data. We performed a systematic review and meta‐analysis of evidence comparing systemic thrombolysis and cardiac surgery in PVT. Methods and Results We searched PubMed, the Cochrane Library, and Embase for studies on treatment strategies in patients with left‐sided PVT since 2000. The primary outcome was death, and the secondary outcomes were major bleeding and thromboembolism during follow‐up (International Prospective Register of Systematic Reviews No. CRD42022384092). We identified 2298 studies, of which 16 were included, comprising 1389 patients with PVT (mean age, 50.4±9.3 years; 60.0% women). Among them, 67.2% were New York Heart Association stage III/IV at admission. Overall, 48.1% were treated with systemic thrombolysis and 51.9% with cardiac surgery. The mortality rate was 10.8% in the thrombolysis group and 15.3% in the surgery group. The pooled risk difference for death with systemic thrombolysis was 1.13 (exact CI, 0.74–1.79; ζ2=0.89; P

Alternative meat (AltMeat), which includes plant-based and cultured meats, has the potential to improve the global food supply chain on numerous environmental and societal dimensions. Some of these gains, derived from lower animal meat consumption, could disrupt the supply chain of crops that are used as animal feed. This study evaluates the potential impact of animal meat displacement on major corn and soybean-producing regions, globally or in developed regions. We combine trading patterns and regional cost structures with potential crop demand reductions caused by animal meat displacement, to occur by 2032 on top of an Organisation for Economic Co-operation and Development and the Food and Agriculture Organization of the United Nations (OECD-FAO) baseline projection without AltMeat. We find that potential animal meat displacement in the US and the European Union (EU) would have a minor effect on crop markets. Worldwide displacement, however, would lead to significantly lower corn and soybean prices relative to the baseline OECD-FAO projection without AltMeat. We explore quantitatively the heterogeneous impact of such developments in crop-producing regions. Our findings shed light on a trade-off associated with the significant benefits of more sustainable meat production.

Introduction: This study described the different stages of uncontrolled hypertension, and assessed independently of the socio-demographic parameters, the non-modifiable and modifiable factors associated with uncontrolled hypertension at ambulatory care, in urban and peri-urban primary health care centres (PHCCs) of Bobo–Dioulasso, Burkina Faso. Methods: A sample of 380 hypertensive adults were consecutively interviewed from January to February 2022, in 20 public PHCCs, in Bobo-Dioulasso. Sociodemographic, non- and modifiable lifestyle, anthropometric and blood pressure parameters were collected. Descriptive, comparative and logistic regression tests were performed. Results: The participants’ mean age was 56.2 ± 10.4 years and frequency of uncontrolled hypertension stage I, II and III was respectively 40.3 %, 23.3 % and 7.9 %. Those with family history of hypertension was 42.4 %. Participants with monotherapy, bi-therapy and tri-therapy represented 51.6 %, 42.6 % and 2.1 % respectively, while 38.2 % declared to be uncompliant with the therapy. About 36 % were current alcohol users, 29.7 % physically inactive, 23.7 % ate less than three servings of fruits and vegetables (FV), 15.3 % were obese, and 12.9 % current tobacco users. In logistic regression analysis, the presence of family history of hypertension [adjusted odds ratio (aOR) = 2.1; p = 0.005], use of bi-/tri-therapy (aOR = 1.7; p = 0.044), daily intake of less than three FV servings (aOR = 1.9; p = 0.025); non-adherence with therapy (aOR = 3.3, p = 0.0001) and obesity (aOR = 4.5; p = 0.003) were associated with uncontrolled hypertension. Conclusion: Uncontrolled hypertension was high at ambulatory primary care. For its efficient management in secondary prevention, a tailored in-hospital strategy including permanent education for a healthier lifestyle practice is needed; and should be complementary strengthened with specific community-based interventions.

Abstract A novel methylation class, “neuroepithelial tumor, with PLAGL1 fusion” (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as “mixed subependymomas-ependymomas” with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.

Abstract Background Disseminated neoplasia (DN) is a proliferative cell disorder of the circulatory system of bivalve mollusks. The disease is transmitted between individuals and can also be induced by external chemical agents such as bromodeoxyuridine. In Mya arenaria, we have cloned and characterized an LTR-retrotransposon named Steamer. Steamer mRNA levels and gene copy number correlates with DN and can be used as a marker of the disease. So far, the only mollusk where a retrotransposon expression relates to DN is Mya arenaria. On the other hand, it has been reported that the Chilean blue mussel Mytilus chilensis can also suffers DN. Our aim was to identify retrotransposons in Mytilus chilensis and to study their expression levels in the context of disseminated neoplasia. Results Here we show that 7.1% of individuals collected in August 2018, from two farming areas, presents morphological characteristics described in DN. Using Steamer sequence to interrogate the transcriptome of M. chilensis we found two putative retrotransposons, named Steamer-like elements (MchSLEs). MchSLEs are present in the genome of M. chilensis and MchSLE1 is indeed an LTR-retrotransposon. Neither expression, nor copy number of the reported MchSLEs correlate with DN status but both are expressed at different levels among individual animals. We also report that in cultured M. chilensis haemocytes MchSLEs1 expression can be induced by bromodeoxyuridine. Conclusions We conclude that SLEs present in Mytilus chilensis are differentially expressed among individuals and do not correlate with disseminated neoplasia. Treatment of haemocytes with a stressor like bromodeoxyuridine induces expression of MchSLE1 suggesting that in Mytilus chilensis environmental stressors can induce activation of LTR-retrotransposon.

We present a comprehensive multi-epoch photometric and spectroscopic study of SN 2024bch, a nearby (19.9 Mpc) Type II supernova (SN) with prominent early high-ionization emission lines. Optical spectra from 2.8 days after the estimated explosion reveal narrow lines of H i , He ii , C iv , and N iv that disappear by day 6. High-cadence photometry from the ground and Transiting Exoplanet Survey Satellite show that the SN brightened quickly and reached a peak M _V ~ −17.8 mag within a week of explosion, and late-time photometry suggests a ^56 Ni mass of 0.050 M _⊙ . High-resolution spectra from days 7.9 and 43 trace the unshocked circumstellar medium (CSM) and indicate a wind velocity of 30–40 km s ^−1 , a value consistent with a red supergiant (RSG) progenitor. Comparisons between models and the early spectra suggest a pre-SN mass-loss rate of $\dot{M}\,\unicode{x0007E}\,1{0}^{-3}\unicode{8210}1{0}^{-2}\,{M}_{\odot }\,{\mathrm{yr}}^{-1}$ , which is too high to be explained by quiescent mass loss from RSGs, but is consistent with some recent measurements of similar SNe. Persistent blueshifted H i and [O i ] emission lines seen in the optical and near-IR spectra could be produced by asymmetries in the SN ejecta, while the multicomponent H α may indicate continued interaction with an asymmetric CSM well into the nebular phase. SN 2024bch provides another clue to the complex environments and mass-loss histories around massive stars.

The gender perspective (GP) aims to generate social change by questioning the stereotypes and roles assigned to individuals and addressing biases and related issues. In Chile, it has been promoted through public policies (Law No.21.369). For this reason, the Physical Education, Sports, and Recreation Pedagogy program at a state university has adjusted its curricular activities. Rhythmic gymnastics (RG), a sport traditionally considered exclusive to women and previously taught only to “them”, must now be taken by all people, regardless of their gender. This research, project funded by the Metropolitan University of Chile DIUMCE01-2024-EFA, analyzes the opinions of 50 students about RG in their curriculum and its relationship with GP prior to taking the course. The study follows a qualitative case study approach, applying semantic content analysis with emergent categories to the responses. The student body presents a favorable attitude toward the curricular activity, expressing interest in applying it within their professional field. They state that sports should be practiced without gender differentiation. They recognize that there are social biases linked to gender stereotypes. On the other hand, the lack of knowledge of RG implies prejudices, such as feeling uncoordinated, inflexible, and uncomfortable when working on corporal expression.

Background: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response. Methods: Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12′s surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome. Results: Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome. Conclusion: This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.

ABSTRACT Objectives Helicobacter pylori gastric infection strongly correlates with gastric diseases such as chronic gastritis, functional dyspepsia, and complications such as peptic ulcers and gastric cancer. In developing countries, systemic therapies are not usually successful due to elevated antibiotic resistance. Additionally, oral H. pylori infection and periodontal disease correlate with gastric treatment failures. This study aimed to explore the effect of an integral therapy, comprising oral hygiene and concomitant systemic treatment, to increase the eradication of gastric infection and recurrences. Materials and Methods A prospective, randomized, four‐arm, parallel‐group, open‐label clinical trial was conducted to investigate the efficacy of integral therapy to eradicate gastric H. pylori infection and avoid recurrences in double‐positive (real‐time PCR oral and gastric infection) patients. Oral hygiene involved mouthwash with neutral electrolyzed water (NEW), with or without periodontal treatment. One hundred patients were equally distributed into four groups: NS, NS‐PT, NEW, and NEW‐PT. All patients had concomitant systemic therapy and additionally, the following oral treatments: mouthwash with normal saline (NS), periodontal treatment and mouthwash with normal saline (NS‐PT), mouthwash with NEW (NEW), and periodontal treatment and mouthwash with NEW (NEW‐PT). Gastric and oral infection and symptoms were evaluated one and four months after treatments. Results Integral therapy with NEW‐PT increased gastric eradication rates compared with NS or NS‐PT (84%−96% vs. 20%−56%; p

ABSTRACT Pseudomonas aeruginosa is a ubiquitous, opportunistic human pathogen. Since it often expresses multidrug resistance, new treatment options are urgently required. Such new treatments are usually assessed with one of the canonical laboratory strains, PAO1 or PA14. However, these two strains are unlikely representative of the strains infecting patients, because they have adapted to laboratory conditions and do not capture the enormous genomic diversity of the species. Here, we characterized the major P. aeruginosa clone type (mPact) panel. This panel consists of 20 strains, which reflect the species’ genomic diversity, cover all major clone types, and have both patient and environmental origins. We found significant strain variation in distinct responses toward antibiotics and general growth characteristics. Only few of the measured traits are related, suggesting independent trait optimization across strains. High resistance levels were only identified for clinical mPact isolates and could be linked to known antimicrobial resistance (AMR) genes. One strain, H01, produced highly unstable AMR combined with reduced growth under drug-free conditions, indicating an evolutionary cost to resistance. The expression of microcolonies was common among strains, especially for strain H15, which also showed reduced growth, possibly indicating another type of evolutionary trade-off. By linking isolation source, growth, and virulence to life history traits, we further identified specific adaptive strategies for individual mPact strains toward either host processes or degradation pathways. Overall, the mPact panel provides a reasonably sized set of distinct strains, enabling in-depth analysis of new treatment designs or evolutionary dynamics in consideration of the species’ genomic diversity.IMPORTANCENew treatment strategies are urgently needed for high-risk pathogens such as the opportunistic and often multidrug-resistant pathogen Pseudomonas aeruginosa. Here, we characterize the major P. aeruginosa clone type (mPact) panel. It consists of 20 strains with different origins that cover the major clone types of the species as well as its genomic diversity. This mPact panel shows significant variation in (i) resistance against distinct antibiotics, including several last resort antibiotics; (ii) related traits associated with the response to antibiotics; and (iii) general growth characteristics. We further developed a novel approach that integrates information on resistance, growth, virulence, and life-history characteristics, allowing us to demonstrate the presence of distinct adaptive strategies of the strains that focus either on host interaction or resource processing. In conclusion, the mPact panel provides a manageable number of representative strains for this important pathogen for further in-depth analyses of treatment options and evolutionary dynamics.

IntroductionAdvanced cutaneous melanoma is a skin cancer characterized by a poor prognosis and high metastatic potential. During metastatic spread, melanoma cells often undergo dedifferentiation toward an invasive phenotype, resulting in reduced expression of microphthalmia-associated transcription factor (MITF)-dependent melanoma antigens and facilitating immune escape. Tumor Necrosis Factor (TNF) is known to be a key factor in melanoma dedifferentiation. Interestingly, accumulating evidence suggests that TNF may play a role in melanoma progression and resistance to immunotherapies. Additionally, TNF has been identified as a potent regulator of sphingolipid metabolism, which could contribute to melanoma aggressiveness and the process of melanoma dedifferentiation.MethodsWe conducted RNA sequencing and mass spectrometry analyses to investigate TNF-induced dedifferentiation in two melanoma cell lines. In vitro experiments were performed to manipulate sphingolipid metabolism using genetic or pharmacologic alterations in combination with TNF treatment, aiming to elucidate the potential involvement of this metabolism in TNF-induced dedifferentiation. Lastly, to evaluate the clinical significance of our findings, we performed unsupervised analysis of plasma sphingolipid levels in 48 patients receiving treatment with immune checkpoint inhibitors, either alone or in combination with anti-TNF therapy.ResultsHerein, we demonstrate that TNF-induced melanoma cell dedifferentiation is associated with a global modulation of sphingolipid metabolism. Specifically, TNF decreases the expression and activity of acid ceramidase (AC), encoded by the ASAH1 gene, while increasing the expression of glucosylceramide synthase (GCS), encoded by the UGCG gene. Remarkably, knockdown of AC alone via RNA interference is enough to induce melanoma cell dedifferentiation. Furthermore, treatment with Eliglustat, a GCS inhibitor, inhibits TNF-induced melanoma cell dedifferentiation. Lastly, analysis of plasma samples from patients treated with immune checkpoint inhibitors, with or without anti-TNF therapy, revealed significant predictive sphingolipids. Notably, the top 8 predictive sphingolipids, including glycosphingolipids, were associated with a poor response to immunotherapy.DiscussionOur study highlights that ceramide metabolism alterations are causally involved in TNF-induced melanoma cell dedifferentiation and suggests that the evolution of specific ceramide metabolites in plasma may be considered as predictive biomarkers of resistance to immunotherapy.

Abstract The number and variety of paints and coating systems in the automotive industry have increased in recent years. However, the basic requirement for the quality of the paints still depends on the surfaces on which they are applied. This applies not only to the large body parts but also to all components that are integrated. There are many surface treatment processes and techniques that are used as an additional process step, such as pickling for a chemical surface treatment or blasting for a mechanical surface treatment. The present work investigates a method for optimizing the surface before painting, using the membrane cup of the ultrasonic sensor as an example for AlMgSi1 alloy, without implementing additional process steps. First, all process steps influencing the surface quality for the production of a membrane cup were considered for optimization. Then, based on a backward process chain analysis, vibratory grinding for deburring of the membrane cup was determined as the process step to be optimized. For the optimization of the vibratory grinding, experiments with two different grindstones were performed. For the characterization of the surface quality, the roughness parameters Rz and Ra were measured with a confocal laser scanning microscope and analyzed in order to determine the optimal process conditions. The experiments showed that the surface roughness can be significantly improved using dedicated process parameters and taking into account the geometry of the vibratory grinding stones. Moreover, different surface qualities can be achieved at different areas on the workpiece, this new approach provides a solution for surface optimization in various areas of the workpiece without additional process steps and costs.

To improve the efficiency of human-robot interaction (HRI) in hazardous ordnance manipulation tasks, the design of an advanced control system for a robotic manipulator needs to be investigated. This article presents a robust finite-time adaptive nonlinear control system designed to address the trajectory tracking control of explosive ordnance disposal (EOD) robotic manipulator, considering the actuator dynamics and subject to external disturbances and uncertainties. First, the theoretical design of the controller is developed. In order to achieve fast convergence, high tracking accuracy, and strong robustness, which are fundamental features in EOD applications, a Backstepping Fast Terminal Sliding Mode Control (BFTSMC) strategy is proposed. The sliding surface coefficients are adaptively tuned in real-time by a neural network, where the backpropagation algorithm updates the neural network weight. The combination of the BFTSMC strategy and the adaptive neural network scheme results in the Adaptive Backstepping Fast Terminal Sliding Mode Control (ABFTSMC) strategy, achieving improved control system performance. The stability of the closed-loop control system is demonstrated using Lyapunov theory to guarantee the convergence of tracking errors to the origin in finite time. Next, a detailed description of the hardware system, encompassing sensors, actuators, and controller boards, is provided for the practical implementation of the ABFTSMC strategy. Finally, the proposed control system is experimentally validated through several tests on a real EOD robotic manipulator, and an extensive comparison analysis with other control approaches is performed. The results evidence that the ABFTSMC strategy demonstrates high robustness, fast convergence in finite time, and good tracking accuracy, which are crucial qualities in real-world EOD applications.

3-D ultrasound reconstruction associated with augmented reality allows physicians to explore a region of interest in 3-D in an intuitive and user-friendly way, while leveraging the advantages of 2D ultrasound imaging: simple, low cost and non-ionizing. It may assist many clinical tasks, such as practician training, procedure assistance or visualization of tissues difficult to interpret through 2D visualization. Recently, new unsupervised deep learning techniques based on a continuous description of the 3-D field, showed promising results in terms of 3-D model estimation, robustness to noise and uncertainty, and efficiency. Inspired by these approaches, the objective of this work is to propose a 3-D ultrasound reconstruction method based on neural implicit representations, adapted to the challenges of an augmented reality pipeline. Results on simulated and experimental data show the precision and efficiency of the reconstruction compared to state-of-the-art neural and traditional reconstructions.

Abstract Background In 2018, the European Medicines Agency authorized adjuvant therapy for patients with resected stage III melanoma. Objectives The objective of the present study (performed in France) was to assess dermatologists' and oncologists' opinions and prescribing habits in this context. Methods From 28 May to 8 June 2021, we performed an online survey of members of the French Groupe de Cancérologie Cutanée (GCC) skin cancer interest group. Results Thirty‐eight practitioners replied to the survey. For BRAF‐mutant melanoma, 58% of the practitioners favoured immunotherapy (IT). If they themselves were to suffer from melanoma with a BRAFV600 mutation, 65% would choose IT for stage IIIB disease, and 72% would choose IT for stage IIID disease. For stage IIIA melanoma with a positive sentinel lymphatic node (SLN) biopsy

Abstract Nanoscale liquid immiscibility is observed in the 2018–2021 Fani Maoré submarine lavas (Comoros archipelago). Heat transfer calculations, Raman spectroscopy, scanning and transmission electron microscopy reveal that in contrast to thin (500 µm) outer rims of homogeneous glassy lava (rapidly quenched upon eruption, >1000 °C s−1), widespread liquid immiscibility is observed in thick (1 cm) inner lava rims (moderately quenched, 1–1000 °C s−1), which exhibit a nanoscale coexistence of Si- and Al-rich vs. Ca-, Fe-, and Ti-rich melt phases. In this zone, rapid nanolite crystallization contrasts with the classical crystallization process inferred for the slower cooled (

Identical quantum particles exhibit only two types of statistics: bosonic and fermionic. Theoretically, this restriction is commonly established through the symmetrization postulate or (anti)commutation constraints imposed on the algebra of creation and annihilation operators. The physical motivation for these axioms remains poorly understood, leading to various generalizations by modifying the mathematical formalism in somewhat arbitrary ways. In this work, we take an opposing route and classify quantum particle statistics based on operationally well-motivated assumptions. Specifically, we consider that a) the standard (complex) unitary dynamics defines the set of single-particle transformations, and b) phase transformations act locally in the space of multi-particle systems. We develop a complete characterization, which includes bosons and fermions as basic statistics with minimal symmetry. Interestingly, we have discovered whole families of novel statistics (dubbed transtatistics) accompanied by hidden symmetries, generic degeneracy of ground states, and spontaneous symmetry breaking – effects that are (typically) absent in ordinary statistics.

Abstract An unresolved issue in contemporary biomedicine is the overwhelming number and diversity of complex images that require annotation, analysis and interpretation. Recent advances in Deep Learning have revolutionized the field of computer vision, creating algorithms that compete with human experts in image segmentation tasks. However, these frameworks require large human-annotated datasets for training and the resulting “black box” models are difficult to interpret. In this study, we introduce Kartezio, a modular Cartesian Genetic Programming-based computational strategy that generates fully transparent and easily interpretable image processing pipelines by iteratively assembling and parameterizing computer vision functions. The pipelines thus generated exhibit comparable precision to state-of-the-art Deep Learning approaches on instance segmentation tasks, while requiring drastically smaller training datasets. This Few-Shot Learning method confers tremendous flexibility, speed, and functionality to this approach. We then deploy Kartezio to solve a series of semantic and instance segmentation problems, and demonstrate its utility across diverse images ranging from multiplexed tissue histopathology images to high resolution microscopy images. While the flexibility, robustness and practical utility of Kartezio make this fully explicable evolutionary designer a potential game-changer in the field of biomedical image processing, Kartezio remains complementary and potentially auxiliary to mainstream Deep Learning approaches.

Abstract Introduction At first interim analysis of KEYNOTE-629, health-related quality of life (HRQoL) with pembrolizumab was stable or improved over 48 weeks in recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). HRQoL results from the second interim analysis in R/M or locally advanced (LA) cSCC are presented. Methods Patients received pembrolizumab 200 mg every 3 weeks for ≤ 2 years. Change in EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EQ-5D-5L scores were exploratory end points. Primary analysis was performed at week 12 to ensure adequate completion/compliance. Descriptive analyses were also conducted through weeks 48 and 75 for the LA and R/M cohorts, respectively. Results At data cutoff (29 July 2020), mean scores in the LA cohort (n = 47) were stable from baseline to week 12 for EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) (−0.27 points [95% confidence interval (CI) −10.93 to 10.39]), physical functioning (−1.29 points [95% CI −8.77 to 6.19]), and EQ-5D-5L visual analog scale (2.06 [95% CI −7.70 to 11.82]). HRQoL remained stable through week 48 in the LA cohort; 76.6% and 74.5% of patients had improved or stable GHS/QoL and physical functioning scores, respectively. HRQoL continued to show stability or improvement through week 75 in the R/M cohort (n = 99); 71.7% and 64.6% of patients had improved or stable GHS/QoL and physical functioning scores, respectively. Conclusions Pembrolizumab has demonstrated antitumor activity and manageable safety. The current analysis shows pembrolizumab treatment preserved HRQoL. Collectively, these results support pembrolizumab as standard of care for LA or R/M cSCC. Trial Registration ClinicalTrials.gov, NCT03284424—September 15, 2017.

Abstract Dinitrogen (N2) fixation provides the major source of reactive nitrogen in the open ocean, sustaining biological productivity. The Indian Ocean (IO) covers 22% of the ocean surface, while it only represents 1% of the global diazotroph database. Hence, constraining the sources of nitrogen in the IO is crucial. Here, we compile three decades of N2 fixation and diazotroph DNA data in the IO. Our analysis reveals basin‐scale yearly rates between ~ 7 and 13 Tg N yr−1. These rates are in the range of previous modeling‐based estimates but may represent a lower bound estimate due to the lack of data in this basin. Diazotroph variability among sub‐basins may suggest endemicity but needs to be taken with caution due to biased sampling toward certain seasons and uneven spatial coverage. We provide recommendations for a more accurate representation of the IO in the global nitrogen budget and our knowledge of diazotroph biogeography.

El objetivo de este trabajo fue conocer las concepciones y estrategias aplicadas por el cuerpo docente de un colegio particular subvencionado de la zona centro-sur de Chile en el proceso de la evaluación formativa durante el periodo de pandemia por Covid-19. Los datos fueron recogidos durante el segundo semestre de 2021. La metodología utilizada tuvo un enfoque cuantitativo, no experimental transversal con alcance descriptivo de tipo exploratorio. Los resultados indican que un 89,4% de la muestra identifica el objetivo de la evaluación formativa de manera correcta, sin embargo, el resto de los docentes tiene una concepción errónea sobre la misma. El 97,9% indica que los estudiantes deben ser participantes activos de la evaluación formativa. Se concluye que, respecto de la evaluación formativa, la mayoría de los docentes maneja e identifica el objetivo, sin embargo, existen docentes que no tienen una concepción correcta de dicha evaluación.

Radon, a naturally occurring radioactive gas, poses a significant health risk by accumulating in buildings and potentially leading to lung cancer. Depending on building construction and geographical location, radon levels can vary substantially both within individual buildings and between different buildings. While previous studies have primarily focused on the impact of temperature and relative humidity on radon devices, the influence of aerosols remains largely unexplored. This paper presents a comprehensive evaluation of the influence of indoor aerosol sources on the performance of real-time radon sensors, encompassing consumer, medium, and research-grade devices. Measurements were performed at relatively low (300 Bq/m3) and high (2′000–3′000 Bq/m3) radon levels in a controlled environment—a stable atomic shelter with constant temperature and humidity conditions. Six different aerosols sources were introduced to produce aerosols of different sizes and concentrations. The results suggest that the tested indoor aerosols did not significantly influence the performance of radon devices, irrespective of their grade or detection method. Consequently, sensor performance and the radon levels being investigated may exert a more significant influence on the obtained results than aerosol levels alone. This paper provides valuable insights into the influence of indoor environment on the performance of radon measuring devices, underscoring the importance of understanding their utility and application scope for researchers, professionals, and the general public alike.

BackgroundCervical Cancer stands as the second leading cause of both incident female cancers and deaths in Burkina Faso. Unfortunately, the prevention, early detection, and care of cervical cancers are suboptimal at individual, institutional, and national levels. In October 2023, we organized a stakeholder’s workshop to develop cervical cancer awareness messaging for disease control in the country.MethodsA one-text workshop was organized with stakeholders working toward improving health in general or women’s health and well-being. A participatory, learning, and adaptive approach was used to facilitate discussions and activities, ensuring the contribution of all participants. Contextual evidence-based and empirical elements about cervical cancer burden and preventive strategies were presented to the participants by key informants. These served as the foundation for a collaborative formulation of messaging content that aimed at raising awareness about cervical cancer.ResultsSixty-two participants from 28 organizations attended the workshop. They work mainly at local and international non-governmental organizations, civil society organizations, universities, university hospitals, research centers, and the Ministry of Health. During the first and second days of the workshop, the participants explored cervical cancer data, its preventive and treatment options available in Burkina Faso, communication strategies for behavioral change, and determinants of the use of prevention and health promotion services. During the following three days, 3 working groups were formed to define strategies, and key messages adapted to diverse tools and targeted audiences. All information was validated during plenary sessions before the end of the workshop and available to all participants and their organizations for cancer awareness activities.ConclusionUpon conclusion of the workshop, the participants provided insightful information for the development of cervical awareness messaging in Burkina Faso. They formed the first community of practice to serve as a dynamic platform for implementation, monitoring, evaluation, and continued learning activities.

Objective Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs).Methods Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis.Results Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5–10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3–6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown.Conclusion EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.

Abstract Electrocatalytic CO2 reduction reaction (CO2RR) offers a sustainable pathway for the production of chemicals and fuels. Acidic electrolysis has been shown to be a promising strategy in order to avoid CO2 loss via the formation (bi)carbonate during reaction. Previous studies have been carried out in ambient CO2 pressure systems and have stressed the importance of adding high concentration of alkali cation (K+) in the catholyte to inhibit the hydrogen evolution reaction (HER) and achieve higher selectivity of CO2RR. Herein, CO2 reduction to HCOOH was performed in strong acid (pH 1) using a dendritic bismuth catalyst in a home‐designed high‐pressure electrochemical cell. At a CO2 pressure of 30 bar, we could achieve a high Faradaic efficiency of 100 % at 100 mA cm−2 at a KCl concentration of 3.0 M. With this first system that combines high pressure of CO2 and highly acidic catholyte, we show that pressurization offers an appropriate strategy to limit both HER and K+ dependence. Indeed we obtained a Faradaic efficiency of 34 % in the absence of K+ cations and 75–80 % in the presence of 1.0 M KCl under an applied current density of 100 mA cm−2.

Sleep disturbances are common in depression, but their neurobiological correlates are poorly understood. Recent evidence suggests links between insula dysfunction and sleep dysregulation. This study aimed to explore the association of sleep quality and structural and functional characteristics of the insula in major depressive disorder (MDD). We included 47 patients with MDD and 15 healthy controls (HC) matched for age and sex. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Patients were classified into two subgroups with poor sleep (PAT-PS, PSQI > 8) and normal sleep (PAT-NS, PSQI ≤ 8), respectively. MRI-scans were acquired using structural and functional resting-state sequences. We analysed cortical thickness of bilateral insulae and connectivity strength of the insula to the whole brain using intrinsic connectivity. Group differences were assessed with a mixed-model MANCOVA controlling for age and sex. Patients had higher PSQI-scores than HC. PAT-PS (n = 21) and PAT-NS (n = 26) did not differ regarding age, sex and depression severity. Insular cortical thickness was reduced in PAT-PS compared to both HC and PAT-NS. Additionally, PAT-PS had lower insular intrinsic connectivity than HC. In contrast, there were no significant group differences in insular intrinsic connectivity between PAT-NS and HC. Across all subjects, PSQI-total was negatively associated with insular cortical thickness and insular intrinsic connectivity. Insular intrinsic connectivity within patients was negatively associated with depression severity. PSQI-total and depression severity did not correlate significantly. In conclusion, our results demonstrate that sleep disturbances in MDD patients are associated with structural and functional impairments of the insula.

BackgroundThe exposure to parasites may influence the immune response to vaccines in endemic African countries. In this study, we aimed to assess the association between helminth exposure to the most prevalent parasitic infections, schistosomiasis, soil transmitted helminths infection and filariasis, and the Ebola virus glycoprotein (EBOV GP) antibody concentration in response to vaccination with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in African and European participants using samples obtained from three international clinical trials.Methods/principal findingsWe conducted a study in a subset of participants in the EBL2001, EBL2002 and EBL3001 clinical trials that evaluated the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against EVD in children, adolescents and adults from the United Kingdom, France, Burkina Faso, Cote d'Ivoire, Kenya, Uganda and Sierra Leone. Immune markers of helminth exposure at baseline were evaluated by ELISA with three commercial kits which detect IgG antibodies against schistosome, filarial and Strongyloides antigens. Luminex technology was used to measure inflammatory and activation markers, and Th1/Th2/Th17 cytokines at baseline. The association between binding IgG antibodies specific to EBOV GP (measured on day 21 post-dose 2 and on Day 365 after the first dose respectively), and helminth exposure at baseline was evaluated using a multivariable linear regression model adjusted for age and study group. Seventy-eight (21.3%) of the 367 participants included in the study had at least one helminth positive ELISA test at baseline, with differences of prevalence between studies and an increased prevalence with age. The most frequently detected antibodies were those to Schistosoma mansoni (10.9%), followed by Acanthocheilonema viteae (9%) and then Strongyloides ratti (7.9%). Among the 41 immunological analytes tested, five were significantly (p < .003) lower in participants with at least one positive helminth ELISA test result: CCL2/MCP1, FGFbasic, IL-7, IL-13 and CCL11/Eotaxin compared to participants with negative helminth ELISA tests. No significant association was found with EBOV-GP specific antibody concentration at 21 days post-dose 2, or at 365 days post-dose 1, adjusted for age group, study, and the presence of any helminth antibodies at baseline.Conclusions/significanceNo clear association was found between immune markers of helminth exposure as measured by ELISA and post-vaccination response to the Ebola Ad26.ZEBOV/ MVA-BN-Filo vaccine regimen.Trial registrationNCT02416453, NCT02564523, NCT02509494. ClinicalTrials.gov.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Abstract Background The postmenopausal period can represent an opportunity for women to improve their health and well-being. The Active and Healthy Ageing in Women during early postmenopause (AHAWOMEN) study aims to identify the key determinants of an active lifestyle among middle-aged women, with a focus on the stages and the social-cognitive variables outlined in the Health Action Process Approach (HAPA) model, a theoretical framework for understanding health behaviour change. We expected that HAPA factors and processes of intention creation (motivational phase) and action adoption (volitional phase) will be significant predictors of exercise initiation and maintenance, supporting both the HAPA tenets and the efficacy of HAPA-based interventions. Methods/design This study was approved by the authors’ Institutional Review Committee. Postmenopausal women aged between 45 and 65 years will voluntarily participate. The participants will be allocated to one of three groups: Intervention-Initiators (n = 100, random allocation), Control-Sedentary (n = 100, random allocation) or Control-Active (n = 100, non-random allocation). The intervention group will engage in a supervised exercise programme lasting at least 3 months, supplemented with a HAPA-based intervention for behaviour change. The sedentary control group will not receive any intervention to change their physical activity, while the active control group will consist of women who are already regularly adhering to an active lifestyle. Study variables will be measured at baseline and postintervention phases, as well as at 1, 3, 6 and 12-month follow-ups. The predictors of exercise behaviour in the different phases of the behavioural change process will be explored and compared within and between groups throughout the study. These analyses will help identify the factors that determine the adoption of a healthy active behaviour. Additionally, the effectiveness of the model and the intervention for changing active behaviour will be evaluated. Discussion This paper describes the rationale, development and methods used in the AHAWOMEN project. Supporting women who intend to become active can help them to translate their goals into sustainable action. Verifying that the HAPA predictions are applicable to postmenopausal women’s adoption of exercise would provide the basis for designing effective interventions for promoting healthy and active ageing that are also tailored to the experiences of middle-aged women. Trial registration ISRCTN16251361. Registration date: 01/06/2023 (retrospectively registered).